Gaucher disease is a disease of glucocerebroside accumulation caused by an autosomal recessive inheritance. The main reason is that deficiency of glucosylceramidase due to mutation of structural gene coding glucosylceramidase results in that glucocerebroside in macrophages cannot be further hydrolyzed and then is accumulated in the lysosome, leading to loss of the original function of the cells, thereby causing diseases in bone, bone marrow, spleen, liver and lung. Eliglustat is a glucosylceramidase inhibitor developed by Genzyme Co. as a subsidiary of Sanofi Co. The US Food and Drug Administration (FDA) approved Eliglustat as an orphan drug on Sep. 17, 2008 and formally approved it to enter the market on Aug. 19, 2014 (Trade name Cerdelga), used as a first-line oral drug for adult patients with Gaucher disease Type 1. According to an article in Journal of the American Medical Association, the oral treatment with Eliglustat resulted in significant improvements in spleen volume, hemoglobin level, liver volume and platelet count in patients with Gaucher disease Type 1.
The chemical name of Eliglustat is N-[(1R,2R)-2-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-hydroxy-1-(pyrrolidinylmethyl)ethyl]octanamide with the structural formula below:
At present, the synthetic routes of Eliglustat mainly include:
Route I. Patent U.S. Pat. No. 7,196,205B2 reported a synthetic route as follows:
Amidation reaction of Intermediate I with Intermediate II produces the desired product.

Intermediate A contains two chiral centers, and this intermediate is a key compound. The synthesis of this compound is the key step described in the patent. The patent specifically described the synthetic steps of intermediate A as follows.

The patent also introduces the method for preparation of intermediate B using N-hydroxysuccimide, and the intermediate B is more advantageous for carrying out the amidation reaction.

However, it is difficult to obtain the raw materials and adjuvants used in the route, the catalyst is expensive, the yield is low and it is difficult to apply the method to industry.
Route II. Patent CN104557851A reported a new synthetic route for synthesis of Eliglustat. The route used intermediate C and intermediate D as the key starting materials and utilized a chiral ligand to build two chiral centers.

The patent also introduces the synthetic methods of intermediate D:
Method 1:
The reaction of pyrrolidine with halo-nitroalkane is used to give intermediate D.

Method 2:
Reduction reaction is used to give intermediate D.

It is difficult to obtain the chiral ligand used in this route, the chiral ligand is expensive, and the key intermediate D is a nitrocompound which has risk of influencing safety in the course of its preparation and use.
Route III. Patent CN105646442A reported a method for preparation of Eliglustat. The route used intermediate G as starting material. After several reaction steps, the reaction with octanoyl chloride finally produces the desired product.

This route only relates to the synthesis from intermediate G to Eliglustat, but does not teach how to synthesize intermediate G. Furthermore, multiple steps of protection and deprotection result in low yield, increased cost and more complicated operations, thus are not advantageous for industrial production.
In order to overcome the defects in the above routes, the present invention provides a new process for synthesis of Eliglustat. The process has advantages of convenient operations, high yield, good purity of intermediates and desired product, and it is easy to apply the process in the industrial production.